Progression of prostate cancer from a subset of p63-positive basal epithelial cells in FG/Tag transgenic mice

Teresita Reiner, Alicia De Las Pozas, Ricardo Parrondo, Carlos Perez-Stable

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Transgenic mice that allow targeting of SV40 T antigen (Tag) to the prostate provide a unique model to identify cancer-initiating cells and follow their progression from a normal cell phenotype into prostate cancer cells. We have developed the FG/Tag transgenic mouse model of prostate cancer using the human fetal globin (FG) promoter linked to Tag. Immunohistochemistry results show that before the development of prostate intraepithelial neoplasia (PIN), a subset of p63+ basal epithelial cells expresses Tag. As in the case of human prostate cancer, there is a loss of p63+ basal cells with neoplastic progression, and a long period of time is required for PIN lesions to develop into palpable prostate tumors. Other immunohistochemistry results show cellular heterogeneity in FG/Tag PIN lesions and primary tumors with neuroendocrine differentiation. Cell lines derived from primary prostate tumors showed characteristics of a neuroendocrine-epithelial intermediate cell type. The FG promoter has high transcriptional activity in intermediate (DU 145, PC-3) and p63+ basal epithelial (LHSR-AR) prostate cancer cells. Therefore, the unexpected development of prostate cancer in the FG/Tag mice may be due to the presence of DNA elements in the FG promoter that can target Tag to specific basal or intermediate cells. We conclude that FG/Tag mouse is a unique model of prostate cancer because the initiating cells are a subset of p63 + basal (possibly stem cells), which may be the true cells of origin for carcinogenesis in aggressive human prostate cancer.

Original languageEnglish (US)
Pages (from-to)1171-1179
Number of pages9
JournalMolecular Cancer Research
Volume5
Issue number11
DOIs
StatePublished - Nov 1 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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